| The frequency dependence of dynamic lung resistance and elastance (R L and EL) for frequencies surrounding breathing are inherently sensitive to the mean level and pattern of obstruction throughout the lung. This dissertation used the frequency dependence of RL and E L to advance our understanding of how emphysema and asthma and their treatments impact lung function.; For emphysema, we first evaluated how the physical extent of tissue degradation relates to functional heterogeneity, or the frequency dependence of R L and EL, and how both would respond to lung volume reduction surgery (LVRS). LVRS is a procedure that removes up to 30% of the lung tissue. We found that RL and EL are elevated in emphysema patients, and EL increases markedly with frequency. These abnormalities did not change significantly after LVRS, indicating that the primary mechanism of improvement from LVRS is a decrease in gas trapping and an increase in static recoil pressure. We also established how specific functional degradation in emphysema related to increases in work of breathing. Using a sheep model, we showed that heterogeneous emphysema caused an elevation in the frequency dependence of RL and EL. As breathing frequency increased, the lung was unable to fully empty during exhalation, resulting in dynamic hyperinflation and a decline in inspiratory capacity. Consequently, the ability of the respiratory system to augment minute ventilation through increases in tidal volume during exercise was limited.; With regard to asthma, we used an antigen challenge to examine how airway inflammation relates to airway reactivity. Immediately after antigen inhalation (early phase), the frequency dependence of RL and EL increased and there was a loss of ability to maximally bronchodilate. About six hours later, a late phase caused a similar, but less severe response that was relieved by a bronchodilator. Active inflammatory cells were not present in early phase, but were elevated during late phase. Our results suggest that inflammation creates a milieu of endogenous bronchoconstrictive mediators that inhibits airway smooth muscle stretching and facilitates its remodeling to a more hypperreactive state. (Abstract shortened by UMI.)... |
